Should MONA Be Used for the Treatment of Acute Coronary Syndrome

Cardiovascular disease (CVD) encompasses illnesses of the heart and blood vessels.¹ Worldwide, amongst all the CVDs, coronary heart disease (CHD) is leading cause of mortality and loss of Disability Adjusted Life Years (DALYs) globally.^2,3 In Canada, approximately 2.6 million people aged 20 and above are diagnosed with heart disease.⁴ Although mortality in patients with known heart disease has decreased by 21% in the last two decades, the burden of CVD on our healthcare system remains high. For instance, in 2021-2022, acute myocardial infarctions (MI) represented 66,078 hospitalizations which corresponded to 2.3% of all inpatient hospitalizations.⁵

Given the prevalence of CVDs in Canada, it is entirely possible for a dentist to manage an emergency associated with this disease process in their career (acute coronary syndrome or ACS). Nowadays, many therapeutic measures exist for the treatment ACS. Nevertheless, when asked about how they would manage this type of critical event, most professionals are likely to remember the mnemonic for morphine, oxygen, nitrates and aspirin or “MONA”. As such, in this article, we will first review the clinical manifestations of CHD before reflecting on the relevance of MONA therapy.

Coronary Heart Disease

CHD is defined as a narrowing of the blood vessels that supply blood and oxygen to the heart. It has several clinical manifestations which could lead to ischemic heart disease (Fig. 1).

Fig. 1: Overview of Cardiovascular Diseases that can Lead to Ischemic Heart Disease

Although these terms are often mistakenly used interchangeably by professionals, there are distinctions to be made. Coronary artery disease (CAD) is the underlying disease process of CHD.^3,6 CAD is characterized by atherosclerotic plaques which cause a narrowing of coronary arteries.^3,6 .As the size of these plaques grows, obstruction of blood flow and decreased coronary blood supply can occur.^3,6 When the myocytes (heart muscle) are poorly perfused by oxygenated blood and an imbalance between supply and demand occurs, myocardial ischemia (cell damage) ensues.^3,6 Ischemic heart disease results from the development of more than 50% narrowing of the lumen of the coronary arteries and/or as a consequence of small vessel of dysfunction in the myocardium, referred to as coronary microvascular disease.³ The acute clinical presentation of CAD (and hence CHD), also known as acute coronary syndrome (ACS), includes myocardial infarction and unstable angina pectoris.³ This condition is what most people describe as having a “heart attack”.

Historically, the origins of CAD can be traced back to Dr. William Heberden who first described angina pectoris in 1768.⁷ Advances in understanding the pathophysiology and developing treatments of CAD were sparse from then until the 20th century. In those years, treatment options for this condition consisted of extended bedrest and other palliative measures.⁷

The first landmark piece of literature describing coronary disease as a potentially treatable thrombotic event was published in 1912.⁸ The advent of coronary angiograms and the creation of catheters meant for selective coronary angiography in the 50s and 60s, paved the way for the first successful percutaneous coronary intervention (PCI) or “stents” in 1977 by Dr. Andreas Grüntzig.⁹ Grüntzig singlehandedly created the field of interventional cardiology which laid the foundations for modern cardiology.¹⁰ PCI has since become the treatment of choice in vascular emergencies, but it is beyond the scope of treatment for dentists.⁹ So, is MONA still relevant for the management of ACS by dentists?

Morphine

Morphine is an opioid that produces most of its analgesic effects by binding to μ receptors.¹¹ Its first documented use for an acute MI can be traced back to Frewen Moore in 1930. In the decades that followed, intravenous (IV) morphine sulfate became routinely used for analgesia in acute MI management.¹² However, with the advances in medicine, the clinical benefits of this medication and its potential harm in the context of ACS have become a subject for debate. Recent cardiac MRI trials found that IV morphine administration prior to PCI in ST-elevation myocardial infarction (STEMI) patients was associated with larger infarct size and suboptimal reperfusion success.¹³ In cases of non-ST-elevation myocardial infarction (NSTEMI), it was reported that individuals who received morphine within the first 24 hours of presentation had greater risks of recurrent MI and higher mortality.¹⁴ Furthermore, it has been shown that morphine delays the absorption and activity of antiplatelet agents in the first hours of ACS.^{15, 16} This means that in the crucial time where drugs like aspirin and P2Y12 inhibitors are used, their benefits are blunted by morphine administration.¹⁵ Therefore, although morphine can be used for pain relief, pain is not associated with mortality. Dental practitioners should exercise caution and not administer it routinely in cases of ACS.

Oxygen

The effects of supplemental oxygen on the cardiovascular system have been studied since the 1940s.⁷ Following several canine animal model studies that showed evidence of reduced myocardial injury, its use became recommended in acute MI.⁷ Unfortunately, data from animal models cannot always be generalized to the human population. In fact, when the first double-blind randomized controlled trial on oxygen therapy for acute MI in humans was published by Rawles et al. in 1976, it showed no benefit in mortality or arrhythmias with 6L/min of oxygen administered throughout 24h.¹⁷ Nowadays, there is mounting evidence demonstrating the potential adverse effects of hyperoxia on the cardiovascular system.¹⁸ Excessive supplemental oxygen could produce paradoxical effects due to increased coronary vascular resistance and reperfusion injury from free radicals.¹⁹ Multiple studies and systematic reviews have shown increased mortality with the use of high-flow oxygen therapy with an increase in recurrent myocardial infarction and infarct size in 6 months.^20,21 Actually, routine use of supplemental oxygen in patients without hypoxemia in the context of suspected MI was not found to reduce 1-year all-cause mortality.²² Therefore, oxygen should be treated like other medical therapies where practitioners seriously consider benefits and side-effects. The use of supplemental oxygen therapy should be encouraged only for hypoxic patients (i.e., oxygen saturation readings below 94%).²⁰

Nitrates

The beneficial effects of nitroglycerin on the symptoms of angina pectoris first appeared in the literature in the 1970s. Although there were concerns that this medication could have detrimental effects due to resulting hypotension,²³ in vivo studies showed its beneficial effects on ischemia by reducing ST-elevation²³ and pulmonary capillary wedge pressure.²⁴ To reduce the incidence of adverse events, this drug is contraindicated when the systolic blood pressure is below 90 mmHg.²⁵ Since then, nitroglycerin has become a commonly used medication in the treatment of chest pain due to its ability to promote vasodilation, resulting in increased blood flow to the heart.²⁶ However, to date, there is a lack of evidence regarding its use in ACS management and potential beneficial effects on clinical outcomes and mortality.⁷ Past randomized-controlled studies have shown that its automatic use, not directed by symptoms, could not improve the rates of mortality or adverse cardiovascular outcomes.^27,28 Additionally, in cases of right ventricular MI (usually confirmed by 12-lead ECG), nitroglycerin can decrease preload to the already compromised right ventricular ejection fraction, which in turn may reduce cardiac output and precipitate hypotension²⁹ leading to lethal repercussions. Therefore, prior to administration, precautions (like positioning the patient in Trendelenburg and providing a fluid challenge if you have intravenous access) should be taken to balance these side-effects with the benefits of secondary analgesia and potential reduced sympathetic stimulation this medication can provide.²⁹

Aspirin

Aspirin is derived from the white willow tree (Salix alba) and is an irreversible inhibitor of the cyclooxygenase-1 (COX-1) receptor, reducing thromboxane A2 and platelet aggregation.⁷ Although it was first studied as a treatment option for MI in the late 1960s, its use did not become commonly accepted until the 80s^30,31 with the publication of the ISIS-2 trial that showed a 23% reduction in cardiovascular mortality in the five weeks after an acute MI.³² Based on evidence from this study and others that followed, the American College of Cardiology Foundation and American Heart Association (ACCF/AHA) then gave aspirin the highest grade of recommendation (Class I) for all patients with acute MI in their guidelines from 1990.³⁰ Hence, aspirin is the only drug in MONA that is a vital component of optimal treatment regimen employed for the management of ACS.³³ Unless otherwise contraindicated, immediate administration of aspirin 162-325 mg (chew and swallow) in patients with pain suggestive of acute myocardial MI is now standard procedure because of the benefits observed in decades of trials.¹⁹

Based on aforementioned information (Fig. 2), it is possible to see that the indiscriminate use of the MONA protocol is not supported by evidence-based medicine and should now be considered obsolete.³³ Based on the newest guidelines from the ACCF/AHA, the novel mnemonic THROMBINS2 (thienopyridines, heparin/enoxaparin, renin-angiotensin system blockers, oxygen, morphine, β-blockers, intervention, nitroglycerin, statin/salicylate) is now used for the treatment of ACS [7]. However, given the clinical context in which most dentists practice and their level of training, it is unrealistic to think that they can employ these strategies in the dental office. As dentists, priority should be given to the prompt transfer of the patient to emergency medical services (EMS) and to the administration of aspirin. While waiting for EMS, supportive measures such as oxygen supplementation could also be considered if the patient becomes hypoxic (< 94%). 

Fig. 2: Summary of MONA Therapy

Oral Health welcomes this original article.

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About the Author:

Dr. Mania Nik Kami completed her DMD at the University of Montreal in 2013. She then practiced general dentistry for 8 years in remote communities of Northern Quebec before coming to Toronto to pursue her MSc degree. She is currently in the Graduate Dental Anesthesia program at the University of Toronto.